Professional Education

  • Doctor of Philosophy, Universitat Graz (2013)
  • Master of Science, Trent College (2009)
  • Bachelor of Science, University Of Pune (2008)

Stanford Advisors

All Publications

  • Distinct roles for IκB kinases alpha and beta in regulating pulmonary endothelial angiogenic function during late lung development. Journal of cellular and molecular medicine Iosef, C., Liu, M., Ying, L., Rao, S. P., Concepcion, K. R., Chan, W. K., Oman, A., Alvira, C. M. 2018; 22 (9): 4410–22


    Pulmonary angiogenesis is essential for alveolarization, the final stage of lung development that markedly increases gas exchange surface area. We recently demonstrated that activation of the nuclear factor kappa-B (NFκB) pathway promotes pulmonary angiogenesis during alveolarization. However, the mechanisms activating NFκB in the pulmonary endothelium, and its downstream targets are not known. In this study, we sought to delineate the specific roles for the NFκB activating kinases, IKKα and IKKβ, in promoting developmental pulmonary angiogenesis. Microarray analysis of primary pulmonary endothelial cells (PECs) after silencing IKKα or IKKβ demonstrated that the 2 kinases regulate unique panels of genes, with few shared targets. Although silencing IKKα induced mild impairments in angiogenic function, silencing IKKβ induced more severe angiogenic defects and decreased vascular cell adhesion molecule expression, an IKKβ regulated target essential for both PEC adhesion and migration. Taken together, these data show that IKKα and IKKβ regulate unique genes in PEC, resulting in differential effects on angiogenesis upon inhibition, and identify IKKβ as the predominant regulator of pulmonary angiogenesis during alveolarization. These data suggest that therapeutic strategies to specifically enhance IKKβ activity in the pulmonary endothelium may hold promise to enhance lung growth in diseases marked by altered alveolarization.

    View details for PubMedID 29993183

  • RNA editing of Filamin A pre-mRNA regulates vascular contraction and diastolic blood pressure. The EMBO journal Jain, M., Mann, T. D., Stulić, M., Rao, S. P., Kirsch, A., Pullirsch, D., Strobl, X., Rath, C., Reissig, L., Moreth, K., Klein-Rodewald, T., Bekeredjian, R., Gailus-Durner, V., Fuchs, H., Hrabě de Angelis, M., Pablik, E., Cimatti, L., Martin, D., Zinnanti, J., Graier, W. F., Sibilia, M., Frank, S., Levanon, E. Y., Jantsch, M. F. 2018


    Epitranscriptomic events such as adenosine-to-inosine (A-to-I) RNA editing by ADAR can recode mRNAs to translate novel proteins. Editing of the mRNA that encodes actin crosslinking protein Filamin A (FLNA) mediates a Q-to-R transition in the interactive C-terminal region. While FLNA editing is conserved among vertebrates, its physiological function remains unclear. Here, we show that cardiovascular tissues in humans and mice show massive editing and that FLNA RNA is the most prominent substrate. Patient-derived RNA-Seq data demonstrate a significant drop in FLNA editing associated with cardiovascular diseases. Using mice with only impaired FLNA editing, we observed increased vascular contraction and diastolic hypertension accompanied by increased myosin light chain phosphorylation, arterial remodeling, and left ventricular wall thickening, which eventually causes cardiac remodeling and reduced systolic output. These results demonstrate a causal relationship between RNA editing and the development of cardiovascular disease indicating that a single epitranscriptomic RNA modification can maintain cardiovascular health.

    View details for DOI 10.15252/embj.201694813

    View details for PubMedID 30087110

  • Loss of PPAR? in endothelial cells leads to impaired angiogenesis. Journal of cell science Vattulainen-Collanus, S., Akinrinade, O., Li, M., Koskenvuo, M., Li, C. G., Rao, S. P., de Jesus Perez, V., Yuan, K., Sawada, H., Koskenvuo, J. W., Alvira, C., Rabinovitch, M., Alastalo, T. 2016; 129 (4): 693-705


    Tie2 promoter-mediated loss of peroxisome proliferator-activated receptor gamma (PPARγ) in mice leads to osteopetrosis and pulmonary arterial hypertension. Vascular disease is associated with loss of PPARγ in pulmonary microvascular endothelial cells (PMVEC), we evaluated the role of PPARγ in PMVEC functions, such as angiogenesis and migration. The role of PPARγ in angiogenesis was evaluated in Tie2CrePPARγ(flox/flox) and wild type (WT) mice, and in mouse and human PMVECs. RNA-sequencing and bioinformatic approaches were utilized to reveal angiogenesis-associated targets for PPARγ. Tie2CrePPARγ(flox/flox) mice showed an impaired angiogenic capacity. Analysis of endothelial progenitor-like cells using bone marrow transplantation combined with evaluation of isolated PMVECs revealed that loss of PPARγ attenuates the migration and angiogenic capacity of mature PMVECs. PPARγ-deficient human PMVECs showed a similar migration defect in culture. Bioinformatic and experimental analyses revealed E2F1 as a novel target of PPARγ in the regulation of PMVEC migration. Disruption of the PPARγ-E2F1 axis was associated with a dysregulated Wnt pathway related to the GSK3β interaction protein. In conclusion, PPARγ plays an important role in sustaining angiogenic potential in mature PMVECs through E2F1-mediated gene regulation.

    View details for DOI 10.1242/jcs.169011

    View details for PubMedID 26743080

  • Activation of the nuclear factor-?B pathway during postnatal lung inflammation preserves alveolarization by suppressing macrophage inflammatory protein-2. American journal of physiology. Lung cellular and molecular physiology Hou, Y., Liu, M., Husted, C., Chen, C., Thiagarajan, K., Johns, J. L., Rao, S. P., Alvira, C. M. 2015; 309 (6): L593-604


    A significant portion of lung development is completed postnatally during alveolarization, rendering the immature lung vulnerable to inflammatory stimuli that can disrupt lung structure and function. Although the NF-κB pathway has well-recognized pro-inflammatory functions, novel anti-inflammatory and developmental roles for NF-κB have recently been described. Thus, to determine how NF-κB modulates alveolarization during inflammation, we exposed postnatal day 6 mice to vehicle (PBS), systemic lipopolysaccharide (LPS), or the combination of LPS and the global NF-κB pathway inhibitor BAY 11-7082 (LPS + BAY). LPS impaired alveolarization, decreased lung cell proliferation, and reduced epithelial growth factor expression. BAY exaggerated these detrimental effects of LPS, further suppressing proliferation and disrupting pulmonary angiogenesis, an essential component of alveolarization. The more severe pathology induced by LPS + BAY was associated with marked increases in lung and plasma levels of macrophage inflammatory protein-2 (MIP-2). Experiments using primary neonatal pulmonary endothelial cells (PEC) demonstrated that MIP-2 directly impaired neonatal PEC migration in vitro; and neutralization of MIP-2 in vivo preserved lung cell proliferation and pulmonary angiogenesis and prevented the more severe alveolar disruption induced by the combined treatment of LPS + BAY. Taken together, these studies demonstrate a key anti-inflammatory function of the NF-κB pathway in the early alveolar lung that functions to mitigate the detrimental effects of inflammation on pulmonary angiogenesis and alveolarization. Furthermore, these data suggest that neutralization of MIP-2 may represent a novel therapeutic target that could be beneficial in preserving lung growth in premature infants exposed to inflammatory stress.

    View details for DOI 10.1152/ajplung.00029.2015

    View details for PubMedID 26163511

    View details for PubMedCentralID PMC4572419

  • The urea decomposition product cyanate promotes endothelial dysfunction KIDNEY INTERNATIONAL El-Gamal, D., Rao, S. P., Holzer, M., Hallstroem, S., Haybaeck, J., Gauster, M., Wadsack, C., Kozina, A., Frank, S., Schicho, R., Schuligoi, R., Heinemann, A., Marsche, G. 2014; 86 (5): 923-931


    The dramatic cardiovascular mortality of patients with chronic kidney disease is attributable in a significant proportion to endothelial dysfunction. Cyanate, a reactive species in equilibrium with urea, is formed in excess in chronic kidney disease. Cyanate is thought to have a causal role in promoting cardiovascular disease, but the underlying mechanisms remain unclear. Immunohistochemical analysis performed in the present study revealed that carbamylated epitopes associate mainly with endothelial cells in human atherosclerotic lesions. Cyanate treatment of human coronary artery endothelial cells reduced expression of endothelial nitric oxide synthase, and increased tissue factor and plasminogen activator inhibitor-1 expression. In mice, administration of cyanate, promoting protein carbamylation at levels observed in uremic patients, attenuated arterial vasorelaxation of aortic rings in response to acetylcholine without affecting the sodium nitroprusside-induced relaxation. Total endothelial nitric oxide synthase and nitric oxide production were significantly reduced in aortic tissue of cyanate-treated mice. This coincided with a marked increase of tissue factor and plasminogen activator inhibitor-1 protein levels in aortas of cyanate-treated mice. Thus, cyanate compromises endothelial functionality in vitro and in vivo. This may contribute to the dramatic cardiovascular risk of patients suffering from chronic kidney disease.

    View details for DOI 10.1038/ki.2014.218

    View details for Web of Science ID 000344446000012

    View details for PubMedID 24940796

  • Acyl Chain-Dependent Effect of Lysophosphatidylcholine on Endothelium-Dependent Vasorelaxation PLOS ONE Rao, S. P., Riederer, M., Lechleitner, M., Hermansson, M., Desoye, G., Hallstroem, S., Graier, W. F., Frank, S. 2013; 8 (5)